Rebecca J Lepping1,2, Robert N Montgomery3, Palash Sharma3, Jonathan D Mahnken2,3, Eric D Vidoni2,4, In-Young Choi1,4, Mark J Sarnak5, William M Brooks1,2,4,6, Jeffrey M Burns2,4,6, Aditi Gupta7,8,9. 1. Hoglund Biomedical Imaging Center, Kansas City, Kansas. 2. University of Kansas Alzheimer's Disease Center, Fairway, Kansas. 3. Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, Kansas. 4. Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas. 5. Division of Nephrology and Hypertension, Department of Internal Medicine, Tufts Medical Center, Boston, Massachusetts. 6. Frontiers: University of Kanas Clinical and Translational Science Institute, University of Kansas Medical Center, Kansas City, Kansas. 7. University of Kansas Alzheimer's Disease Center, Fairway, Kansas agupta@kumc.edu. 8. Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas. 9. The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas.
Abstract
BACKGROUND: CKD is associated with abnormalities in cerebral blood flow, cerebral neurochemical concentrations, and white matter integrity. Each of these is associated with adverse clinical consequences in the non-CKD population, which may explain the high prevalence of dementia and stroke in ESKD. Because cognition improves after kidney transplantation, comparing these brain abnormalities before and after kidney transplantation may identify potential reversibility in ESKD-associated brain abnormalities. METHODS: In this study of patients with ESKD and age-matched healthy controls, we used arterial spin labeling to assess the effects of kidney transplantation on cerebral blood flow and magnetic resonance spectroscopic imaging to measure cerebral neurochemical concentrations (N-acetylaspartate, choline, glutamate, glutamine, myo-inositol, and total creatine). We also assessed white matter integrity measured by fractional anisotropy (FA) and mean diffusivity (MD) with diffusion tensor imaging. We used a linear mixed model analysis to compare longitudinal, repeated brain magnetic resonance imaging measurements before, 3 months after, and 12 months after transplantation and compared these findings with those of healthy controls. RESULTS: Study participants included 29 patients with ESKD and 19 controls; 22 patients completed post-transplant magnetic resonance imaging. Cerebral blood flow, which was higher in patients pretransplant compared with controls (P=0.003), decreased post-transplant (P<0.001) to values in controls. Concentrations of neurochemicals choline and myo-inositol that were higher pretransplant compared with controls (P=0.001 and P<0.001, respectively) also normalized post-transplant (P<0.001 and P<0.001, respectively). FA increased (P=0.001) and MD decreased (P<0.001) post-transplant. CONCLUSIONS: Certain brain abnormalities in CKD are reversible and normalize with kidney transplantation. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to mitigate them even in patients who cannot be transplanted. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Cognitive Impairment and Imaging Correlates in End Stage Renal Disease, NCT01883349.
BACKGROUND: CKD is associated with abnormalities in cerebral blood flow, cerebral neurochemical concentrations, and white matter integrity. Each of these is associated with adverse clinical consequences in the non-CKD population, which may explain the high prevalence of dementia and stroke in ESKD. Because cognition improves after kidney transplantation, comparing these brain abnormalities before and after kidney transplantation may identify potential reversibility in ESKD-associated brain abnormalities. METHODS: In this study of patients with ESKD and age-matched healthy controls, we used arterial spin labeling to assess the effects of kidney transplantation on cerebral blood flow and magnetic resonance spectroscopic imaging to measure cerebral neurochemical concentrations (N-acetylaspartate, choline, glutamate, glutamine, myo-inositol, and total creatine). We also assessed white matter integrity measured by fractional anisotropy (FA) and mean diffusivity (MD) with diffusion tensor imaging. We used a linear mixed model analysis to compare longitudinal, repeated brain magnetic resonance imaging measurements before, 3 months after, and 12 months after transplantation and compared these findings with those of healthy controls. RESULTS: Study participants included 29 patients with ESKD and 19 controls; 22 patients completed post-transplant magnetic resonance imaging. Cerebral blood flow, which was higher in patients pretransplant compared with controls (P=0.003), decreased post-transplant (P<0.001) to values in controls. Concentrations of neurochemicals choline and myo-inositol that were higher pretransplant compared with controls (P=0.001 and P<0.001, respectively) also normalized post-transplant (P<0.001 and P<0.001, respectively). FA increased (P=0.001) and MD decreased (P<0.001) post-transplant. CONCLUSIONS: Certain brain abnormalities in CKD are reversible and normalize with kidney transplantation. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to mitigate them even in patients who cannot be transplanted. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Cognitive Impairment and Imaging Correlates in End Stage Renal Disease, NCT01883349.
Authors: Dorothea Nitsch; Morgan Grams; Yingying Sang; Corri Black; Massimo Cirillo; Ognjenka Djurdjev; Kunitoshi Iseki; Simerjot K Jassal; Heejin Kimm; Florian Kronenberg; Cecilia M Oien; Andrew S Levey; Adeera Levin; Mark Woodward; Brenda R Hemmelgarn Journal: BMJ Date: 2013-01-29
Authors: Manjula Kurella Tamura; Sarah Gaussoin; Nicholas M Pajewski; Greg Zaharchuk; Barry I Freedman; Stephen R Rapp; Alexander P Auchus; William E Haley; Suzanne Oparil; Jessica Kendrick; Christianne L Roumie; Srinivasan Beddhu; Alfred K Cheung; Jeff D Williamson; John A Detre; Sudipto Dolui; R Nick Bryan; Ilya M Nasrallah Journal: Am J Kidney Dis Date: 2021-09-17 Impact factor: 11.072